Many patients have a need for substantially continuous or real-time monitoring of levels of substances in their body fluids. For example, diabetic patients are advised to check their blood glucose level periodically to ensure that their blood glucose level is at a value that is within a safe range so as to avoid hyperglycemic and hypoglycemic conditions. Large fluctuations in blood glucose level indicate that a patient may need to take corrective action immediately to prevent a medical emergency, such as loss of consciousness. The corrective action typically involves receiving a dose of insulin or ingesting fast acting carbohydrates. To determine blood glucose level, a diabetic patient often utilizes a blood glucose meter (also referred to as a blood glucose monitor or “BGM”). The BGM provides a measured blood glucose level based on a blood sample of the patient. The blood sample is obtained by the patient or caregiver, such as by a finger stick, usually with the assistance of a lancing device. The device lances the skin of the patient, drawing out a small quantity of capillary blood that is then placed on a test strip for analysis by the BGM. To properly monitor a patient's blood glucose level, lancing may be performed by the patient or caregiver at regular time intervals that are dependent of the severity of the diabetes. Each lancing can be uncomfortable. Such discomfort motivates many patients to decrease the frequency of using this method to measure their blood glucose level, which may result in inadequate monitoring and, ultimately, improper insulin dosage. Similarly, variance in the accuracy of the test strips commonly used with BGMs can cause errors in the measured blood glucose level for a patient, which again which may ultimately result in improper insulin dosage due to reliance thereon.
A second type of glucose meter, a continuous glucose monitor (CGM), provides a substantially continuous estimated blood glucose level through a transcutaneous sensor that measures analytes, such as glucose, in the patient's interstitial fluid rather than their blood. Examples of CGMs include the Seven®, Seven® PLUS, and G4™ Platinum monitoring systems sold by Dexcom®, Inc. of San Diego, Calif. CGM systems typically consist of a transcutaneously-placed sensor, a transmitter, and a monitor (either a stand-alone monitor or one built into an insulin pump). Such systems and definitions of related terms are described in greater detail in, e.g.: U.S. Pat. Nos. 8,311,749; 7,711,402; and 7,497,827; each of which is hereby incorporated by reference in its entirety. A CGM system allows a patient or caregiver insert a single sensor probe under the skin for multiple days, such as for a week. Thus, the patient is only required to perform a single moderately invasive action with a single entry point in the subdermal layer on, e.g., a weekly basis. Because the CGM estimates blood glucose levels from analyzing interstitial plasma or fluid rather than blood as with BGMs, however, CGMs generally are not as well-suited for accurate blood glucose monitoring. Accordingly, CGMs are most often used for identifying trends in blood glucose levels over time and for providing estimates thereof. It is necessary to calibrate the CGM sensor's measurement of a patient's interstitial fluid to an estimated blood glucose level. For example, a voltage output or current output value of the sensor that is generated from exposure to the interstitial fluid of a patient is associated with a corresponding blood glucose level of the patient. A calibration curve defines the function that generates an estimated blood glucose level (typically provided in, e.g., mg/dL or mmol/L) for a given sensor output value (typically provided in, e.g., volts, amperes, coulombs or other output values; some values are based on optical sensors). A CGM may utilize a predetermined calibration curve that is based on collected sensor output data and corresponding blood glucose levels determined for a general patient population. With some devices, the calibration curve can be adjusted for measured blood glucose levels taken for an individual patient (e.g., via a lancing device).
A CGM, such as a portable CGM, may be incorporated with other components to provide useful medical systems. One such component is a medical infusion device used for the administration of substances such as medicaments directly into the body of a patient. Ambulatory insulin pumps are a type of portable medical infusion device that administer insulin to those diagnosed with both Type I and Type II diabetes. Portable insulin pumps are effective in the treatment of diabetes and offer an alternative to multiple daily injections of insulin via an insulin syringe or an insulin pen. Portable insulin pumps also allow for continuous insulin therapy. The continuous administration of insulin may be particularly helpful in the treatment of diabetes, where a large percentage of patients depend on the delivery of a known amount of insulin at predetermined intervals. The administration of insulin for a diabetic patient is one of a few medical indications in which the patient routinely administers the medicament to themselves by a subcutaneous modality, such as via a hypodermic syringe injection. An insulin pump provides a patient with an alternative to syringe injection for safely, reliably, and comfortably administering required doses of medication at appropriate times.
Ambulatory insulin infusion pumps, such as the T:slim® pump sold by Tandem Diabetes Care, Inc. of San Diego, Calif., the Paradigm® Revel™ pump sold by Medtronic Minimed, Inc. of Northridge, Calif., and the One Touch® Ping® pump sold by Animas Corporation of West Chester, Pa., typically allow the patient or caregiver to adjust the amount of insulin delivered, by a basal rate or a bolus, based on blood glucose data obtained by a BGM or CGM. Some ambulatory insulin infusion pumps may include the capability to interface with a BGM or CGM such as, e.g., by receiving measured or estimated blood glucose levels and prompting the user to adjust the level of insulin being administered or planned for administration or, in cases of abnormally high blood glucose readings, prompting temporary cessation of insulin administration. These portable pumps may incorporate a BGM or CGM within its hardware or may communicate with dedicated BGM or CGMs via, wired or wireless data communication protocols. Such pumps may be particularly important in facilitating patient compliance and improved or more accurate treatment of the condition. Other portable pumps being developed have the ability for the automatic control of medicament delivery based on, e.g., CGM sensor data. The delivery of insulin from a portable insulin pump making use of CGM data necessitates accurate and reliable CGM output.
In a CGM system, whether of the dedicated, “stand-alone” system or one that is incorporated with a medical device such as a portable insulin pump, the calibration of the CGM sensor may drift over time. The drift may occur as a result of, for example, aging of the sensor and reaction of the patient's body to the sensor probe itself. Because of this drift, it is necessary to update or adjust a calibration curve after a user has inserted the CGM sensor probe to obtain the most accurate estimates possible. The calibration curve of a CGM system can be updated by obtaining a measured blood glucose level, such as via a BGM that utilizes a sample of a patient's blood, and entering the measured blood glucose level into the CGM. The CGM can compare its sensor output value at a particular time with the measured blood glucose level obtained at substantially the same time and adjust its calibration curve to reflect the obtained measured blood glucose level. The adjustment may utilize, for example, linear regression techniques for data analysis, to produce an adjusted calibration curve. Generally, a calibration of the CGM with a measured blood glucose level is recommended at least once every twelve hours, as the sensor drift can become relatively more significant at greater time intervals.
Sensor drift, and the need for calibration, can be more pronounced if a patient does not follow the recommended sensor change schedule. As noted, most CGM systems, whether a dedicated CGM or one that is incorporated in a medical device such as a portable insulin pump, utilize a sensor probe that is placed under the skin for a period of days, e.g., approximately seven days, after which the sensor probe is replaced with a new sensor probe. Patients may, however, leave a sensor probe in place for a longer time, to decrease the frequency of performing the insertion procedure. A sensor probe that has remained unchanged in a patient for a longer time period may experience increased output drift. In other cases, the sensor drift may occur at a higher rate early in its life, depending upon a variety of factors.
Although CGM calibration via a measured blood glucose level is useful for correcting the correlation of the CGM device sensor output to blood glucose level at the time of calibration, sensor drift can cause a sensor output reading at a time between calibrations to vary, even significantly vary, from what a measured blood glucose level would be if taken at approximately the same time. Therefore, there is a need for a CGM that can be more effectively calibrated to provide more accurate estimates of blood glucose level.